Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma

Palumbo, Antônio; Cavallo, Federica; Raimondo, Francesco Di; Larocca, Alessandra; Hardan, Izhar; Nagler, Arnon; Petrucci, Maria Teresa; Hájek, Roman; Pezzatti, Sara; Delforge, Michel; Patriarca, Francesca; Donato, F.; Cerrato, Chiara; Nozzoli, Chiara; Yu, Zhinuan; Boccadifuoco, Luana; Caravita, Tommaso; Benevolo, Giulia; Guglielmelli, Tommasina; Vincelli, Donatella; Jacques, Christian; Dimopoulos, Meletios Α.; Ciccone, Giovannino; Musto, Pellegrino; Corradini, Paolo; Cavo, Michèle; Boccadoro, Mario

doi:10.1200/jco.2014.60.2466

Cited by 140 publications

(87 citation statements)

References 28 publications

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“…A similar post hoc approach has been used in other trials of maintenance therapy in transplant-ineligible NDMM patients. 12, 13 Palumbo et al 13 pooled data from two phase III trials comparing continuous therapy with fixed-duration therapy and found that median PFS2 was significantly longer with continuous therapy (63 vs. 47 months; HR 0.69; P=0.0001). In an exploratory analysis of the largest prospective randomized trial conducted in NDMM patients (FIRST trial), Benboubker et al 12 similarly reported a significant improvement in median PFS2 with continuous lenalidomide and dexamethasone therapy compared with a fixed-duration regimen of melphalan, prednisone, thalidomide (42.9 vs. 36.3 months; HR 0.78; P=0.005).…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

et al. 2015

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

et al. 2015

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“…7 The increasing availability of drugs with well-balanced efficacy and toxicity profiles has led to the design of more complex and prolonged treatment strategies, 8,9 but it has also raised the unmet need for surrogate markers to predict overall survival (OS) and accelerate the approval of new agents. 10 Thus, there is a growing body of evidence indicating that minimal residual disease (MRD) assessment can potentially be used as a biomarker to evaluate the efficacy of different treatment strategies and potentially act as surrogate for OS, particularly among transplant-eligible patients 11,12 ; however, it is perhaps in elderly MM patients, the most common subgroup and for which an optimal balance between efficacy and toxicity is of utmost importance, that sensitive response assessment could help to avoid under-or overtreatment.…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

Paiva

Cedena

Puig

et al. 2016

Blood

136

116

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Key Points• MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespective of age or cytogenetic risk.• Second-generation MFC immune profiling concomitant to MRD monitoring also helped to identify patients with different outcomes.The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first-to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10 25; n 5 54, 34%), MRD positive (between <10 24and ‡10 25 ; n 5 20, 12%), and MRD positive ( ‡10 24 ; n 5 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P 5 .007) and overall survival (OS) (HR, 3.1; P 5 .04), with significant benefit for MRDnegative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10 24 and ‡10 25 vs ‡10 24 (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P 5 .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P 5 .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249. (Blood. 2016;127(25):3165-3174)

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“…A meta-analysis of three trials, one of which included ASCT as part of consolidation, demonstrated improved PFS1, PFS2 (time to second progression of death), and OS with continuous therapy. In fact, a prolonged PFS1 did not reduce PFS2 62 . In conclusion, novel agent-based triplet induction, front-line early ASCT, and maintenance therapy remain the preferred strategy for transplant-eligible patients.…”

Section: Transplant Still Bettermentioning

confidence: 86%

Recent advances in understanding multiple myeloma

2016

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There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents) in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

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Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma

Cited by 140 publications

References 28 publications

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

Recent advances in understanding multiple myeloma

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